The cancer preventive activity and mechanisms of prenylated resveratrol and derivatives

Resveratrol is regarded as neutraceuticals with multiple health benefits. The introduction of prenyl can enhance the bioactivity. In this work, the cancer preventive activities and mechanisms of 18 prenylated reseveratrol and derivatives were investigated. The results showed that prenyl increased the antiproliferative activities of resveratrol, oxyresveratrol and piceatannol against cancer cells, and their antiproliferative activities were time- and dose-dependent. 4-C-prenylation was important for the antiproliferative activity of stilbenoids. The 4-C-prenyl stilbenoids showed better antiproliferative activities than other prenylated stilbenoids. 4-C-prenyl piceatannol showed the best antiproliferative activity. Human hepatoellular carcinomas (HepG₂) cell was more sensitive to prenylated stilbenoids than human MCF-7 breast carcinoma cell. 4-C-prenyl piceatannol had high affinities to Caspase-3, Caspase-9, CDK2 and Cyclin A2. The possible amino acids involved in binding 4-C-prenyl piceatannol were revealed. The expression of Caspase-3 and Caspase-9 were upregulated by 4-C-prenyl piceatannol and the expression of CDK2 and Cyclin A2 in HepG₂ cells were downregulated, which contributed to apoptosis. The above results eludicated the possible antiproliferative mechanisms of prenylated stilbenoids.